Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model.

Abstract

Neuroinflammation plays an important role in the progression of Parkinson's disease (PD) and hence may represent a target for treatment. The drugs used currently for PD only provide symptomatic relief and have adverse effects in addition to their inability in preventing degeneration of neurons. Flavonoids show potent antioxidant and anti-inflammatory activities which is very valuable for the health of human beings. Thus, in the present study, we have tried to explore the anti-inflammatory activity of orally given ursolic acid (UA) (25 mg/kg bwt), a pentacyclic triterpenoid in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model. Significant severe oxidative stress and biochemical alterations have been seen in Parkinsonian mice after MPTP intoxication. Whereas, UA administration has significantly rescued the harmful consequence of MPTP intoxication. Ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor-κB (NF-κB) were seen to be altered in the substantia nigra pars compacta (SNpc) of MPTP-intoxicated mice through immunohistochemical studies. The changes in the expression level of these parameters primarily suggest increased inflammatory responses in MPTP-intoxicated mice as compared with the control. However, UA have significantly reduced these inflammatory parameters (Iba1 and TNF-α) along with transcription factor NF-κB, which regulates these inflammatory parameters and thus have inhibited MPTP-induced neuroinflammation. The immunoreactivity of tyrosine hydroxylase (TH) was considerably increased by UA treatment in the SNpc of Parkinsonian mice. The neuroinflammation and neurodegeneration along with impairments in biochemical and behavioral parameters were found to be reversed on treatment with UA. Thus, UA has shown potent anti-inflammatory activity by preventing the degeneration of dopaminergic neurons from MPTP-induced Parkinsonian mice.

• Authors: Sachchida Nand Rai, Walia Zahra, Saumitra Sen Singh, Hareram Birla, Chetan Keswani, Hagera Dilnashin, Aaina Singh Rathore, Rajan Singh, Rakesh K Singh, Surya Pratap Singh
• Journal: Neurotoxicity research (Neurotox Res) Vol. 36 Issue 3 Pg. 452-462 (Oct 2019) ISSN: 1476-3524 [Electronic] United States
• PMID: 31016688 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antiparkinson Agents
• Nitrites
• Triterpenes
• Malondialdehyde
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Catalase
• Glutathione

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antiparkinson Agents (therapeutic use)
• Brain (drug effects, metabolism)
• Catalase (metabolism)
• Fluorescent Antibody Technique
• Glutathione (metabolism)
• Inflammation (drug therapy)
• Lipid Peroxidation (drug effects)
• Male
• Malondialdehyde (metabolism)
• Mice
• Nitrites (metabolism)
• Parkinsonian Disorders (chemically induced, drug therapy)
• Psychomotor Performance
• Real-Time Polymerase Chain Reaction
• Rotarod Performance Test
• Triterpenes (therapeutic use)
• Ursolic Acid